We are studying the assembly of bacterial viruses, by identifying the genes and proteins involved in assembly processes, and the protein-protein interaction which result in the formation of complex structure. The experiments concentrate on 1) the formation of the head of the temperate generalized transducing phage P22 of Salmonella and 2) on the assembly of the contractile tail of bacteriophage T4, and 3) assembly of the tail of phage lambda. Of particular interest in P22 assembly is the participation of a catalytic scaffolding protein in shell formation. Scaffolding protein copolymerizes with coat protein to yield a precursor shell containing both proteins. In concert with DNA packaging all the scoffolding molecules exit from the precursor shell and then recycle to catalyze further shell assembly. The assembly of the phage tail requires the products of 21 phage genes. We are trying to identify all the morphological intermediates in tail assembly and the nature of the sequential assembly process. All the reactions proceed in vitro, providing a very useful activity assay for structural proteins. The proteins seem to be synthesized in a form in which they don't spontaneously assemble. There is no proteolytic cleavage; rather the proteins are activated by incorporation into a preformed intermediate structure, which then becomes the active substrate for the next protein in the pathway. We would like to use the phage assembley reactions as a system to study chemicals which inhibit protein-protein interaction. BIBLIOGRAPHIC REFERENCES: King, J., Botstein, D., Casjens, S., Earnshaw, W., harrison, S., and Lenk, E. (1976). Structure and Assembly of the Capsid of Bacteriophage P22. Proc. Roy. Soc., London, Series B., in press. Kikuchi, Y., and King, J. (1976). Assembly of the Contractile Tail of Bacteriophage T4, in "Cell Motility". Cold Motility". Cold Spring Harbor Laboratory, NY., in press.